This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the University of Duisburg-Essen in Germany. Today, I would like to report on five exciting studies from March 2022.
Cell Therapy for Duchenne Muscular Dystrophy
I would like to start with what I consider a landmark paper in The Lancet about the future therapy of Duchenne muscular dystrophy. You all know this disease, which is progressive atrophy and paralysis of muscles first in the lower and then in the upper extremities, and accompanying cardiomyopathy. Today, the life expectancy for this disease is about 20-40 years. There is now a new gene therapy, but we definitely need also alternative therapies.
This paper describes the use of cardiosphere-derived stem cells, which have been used in the past for the treatment of cardiac failure. These cells have immunomodulatory, antifibrotic, and regenerative effects. The mode of action most probably occurs via exosomes.
In this placebo-controlled trial, patients with Duchenne muscular atrophy and upper-extremity motor function limitations received either cell therapy (eight patients) or placebo (12 patients) every 3 months for 1 year. The patients who received the real treatment showed an improvement of upper-limb function, whereas those treated with placebo showed a deterioration. This treatment was relatively well tolerated. Three patients had hypersensitivity reactions.
If this turns out in a larger and longer trial to be an effective therapy, it would really be a breakthrough for the treatment of muscular dystrophy.
A First-in-Human Treatment Study in Creutzfeldt-Jakob Disease
The second paper, which was also published in The Lancet, deals with prion diseases, including Creutzfeldt-Jakob disease. This is also a disease you’re familiar with. Prions are misfolded proteins, and they act like an infectious agent that distributes itself throughout the brain.
A research group in the United Kingdom developed human monoclonal antibodies against the prion protein. They treated six patients with Creutzfeldt-Jakob disease. Their results indicated that these treatments could work well. At the end of the day, all of these patients died. But in two patients in whom neuropathologic examination was possible, researchers could show that the antibody is present in the brain at areas where you expect it to be.
What is the future potential of this treatment? I think the most important would be in the hereditary prion diseases to see whether if you treat patients who start to show symptoms, you can slow the disease using these monoclonal antibodies.
Aducanumab’s High-Profile Stumble
The third paper, published in the Journal of Prevention of Alzheimer’s Disease, deals with a very controversial issue: the use of aducanumab in early Alzheimer’s disease. This is a drug that is a monoclonal antibody against amyloid beta. And now, finally, two phase 3 studies were published.
These were trials in patients with early Alzheimer’s disease proven by amyloid PET criteria. Each of these studies had over 1600 patients, and they were terminated prematurely owing to futility when 50% of the patients were recruited. The company then performed a post hoc analysis and found a positive result in one of the studies and a neutral result in the other one.
This led the US Food and Drug Administration to approve this treatment. The European Medicines Agency has rejected the approval of this drug.
The problem is that the benefit, if there is any, is small. And 30% of patients develop brain edema, which can be shown on MRI. This means that in addition to the high cost of the treatment, these patients have to undergo MRI on a regular basis. Whether these high costs are really justified, compared with the small benefit that is seen, is really questionable, I think.
Post-Stroke Cardiac Rhythm Monitoring
The next study was published in Neurology and deals with long-term ECG monitoring after stroke or transient ischemic attack to identify silent paroxysmal atrial fibrillation. The authors performed a meta-analysis of eight trials — five randomized trials and three observational studies, with approximately 3000 patients — where long-term ECG monitoring, usually with implantable devices, was compared with standard of care, which is intermittent EEG recordings.
They observed, unsurprisingly, a two to four times higher probability of detecting atrial fibrillation with implantable loop recorders. But unfortunately, this did not result in a reduction in the risk for stroke. This could be a question of statistical power. But the consequence in some European countries, unfortunately, is that the healthcare providers now refuse to pay for implantable loop recorders.
Direct Oral Anticoagulants (DOACs) vs Warfarin
The last study was published in Stroke and deals with cerebral sinus venous thrombosis. You all know that in the acute phase of this disease, patients are treated with heparin or low-molecular-weight heparin. Until now, long-term treatment was warfarin to prevent recurrent thrombosis and to promote recanalization.
The authors did an observational study, looking at all together more than 800 patients with cerebral sinus venous thrombosis. Of these patients, 33% received DOACs (eg, dabigatran, rivaroxaban, or apixaban), 52% received warfarin, and the remaining patients received both.
Researchers observed a rate of recurrent venous thrombosis of 5.7% per year, 3.8% major bleeding complications, and 1.8% mortality. In terms of recurrent thrombosis, recanalization, and death, there was no difference between DOACs and warfarin. But the risk for major bleeding was reduced by 65% for DOACs over warfarin. This would be a very strong argument to use DOACs in patients with cerebral sinus venous thrombosis.
Dear colleagues, ladies and gentlemen, thank you very much for listening and watching about these five exciting studies from March 2022.